Letter to the Editor. Is aspirin a new silver bullet for reducing the growth of intracranial aneurysms?

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  • 1 Institute of Neurosciences, Universidad Austral de Chile, Valdivia, Chile
  • 2 Wexner Medical Center, The Ohio State University, Columbus, OH
  • 3 Neurosciences Centre, AIIMS, New Delhi, India
  • 4 Center of Biomedical Research (CIB), University of Cartagena, Cartagena de Indias, Colombia
  • 5 All India Institute of Medical Sciences, Madhya Pradesh, India
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TO THE EDITOR: We read with great interest the research by Zanaty et al.1 (Zanaty M, Roa JA, Nakagawa D, et al. Aspirin associated with decreased rate of intracranial aneurysm growth [published online October 29, 2019]. J Neurosurg. doi:10.3171/2019.6.JNS191273) and we congratulate the authors for figuring out a solution for the management of relatively smaller unruptured intracerebral aneurysms, as literature had hypothesized earlier.2 The article is well written, and the authors have demonstrated that aspirin administration is associated with decreased growth of unruptured intracranial aneurysms. We note that aspirin is a well-known drug that is widely used in clinical praxis for an extensive variety of indications including the prevention of cardiovascular events.3 Hudson et al. showed evidence of aspirin reducing the rate of growth of aneurysms. COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E2 synthase–1) are both inhibited by aspirin. These substances have a crucial role in aneurysm pathogenesis.4 However, there is a more complex interaction among aspirin, smoking, hypertension, and cerebrovascular diseases, including the increased risk of cerebral aneurysm growth. Smoking is known to exacerbate hypertension, stroke, pulmonary disease, heart diseases, and atherosclerosis.5 Smoking also exacerbates hypertension—with increased risk of malignant, renovascular hypertension6—as well as being a risk factor for intracranial aneurysm rupture.7

We want to highlight some important issues that this study raises. First, there is the inability to measure the smoking status of the studied cohort and the impact of smoking on aneurysm growth. Second, there is limited analysis of the role of hypertension in the growth of the aneurysm. Also, based on recall bias, it is not clear why only the smoking risk factor was excluded and no other parameters were treated and interpreted similarly. It is necessary to distinguish recall bias from simply inaccurate information; several studies suggest that there is a greater likelihood of recall bias when recall is poor, which constitutes the majority of cases.8 It is important to consider that if a patient had a recall bias for smoking, then this same patient would have a recall bias for other events as well (of course this assumption may not be true, but it is possible). Another very important point is the conclusion of Zanaty et al.’s article, namely: “However, smoking is not part of the PHASES [population, hypertension, age, size of aneurysm, earlier SAH from another aneurysm, and site of aneurysm] clinical score.” This finding from the PHASES clinical score needs to be interpreted with caution. Bijlenga et al.9 and Greving et al.10 showed that cumulative risk factors did not add value to prediction of aneurysm rupture. However, the authors also did not rule out the role of individual factors as an independent predictor of outcome. The authors further suggested that a change in smoking behavior (e.g., cessation) was probably one reason for the absence of risk effect on aneurysm rupture. The authors further suggested that the effect of continued smoking should not be interpreted as neutral for assessing the risk factors for intracranial aneurysm rupture.4 Zanaty et al. should be commended and thanked for this innovative treatment. However, detailed analysis of smoking behavior should be performed objectively while assessing various risk factors for growth of cerebral aneurysms. In that respect, definitely, a very well-recognized risk factor in such diseases must not be skipped.

Disclosures

The authors report no conflict of interest.

References

  • 1

    Zanaty M, Roa JA, Nakagawa D, Aspirin associated with decreased rate of intracranial aneurysm growth [published online October 29, 2019]. J Neurosurg. doi:10.3171/2019.6.JNS191273

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  • 2

    Starke RM, Chalouhi N, Ding D, Hasan DM. Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage. Cerebrovasc Dis. 2015;39(5–6):332342.

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  • 3

    Russo NW, Petrucci G, Rocca B. Aspirin, stroke and drug-drug interactions. Vascul Pharmacol. 2016;87:1422.

  • 4

    Hudson JS, Marincovich AJ, Roa JA, Aspirin and intracranial aneurysms. Stroke. 2019;50(9):25912596.

  • 5

    Timmreck TC, Randolph JF. Smoking cessation: clinical steps to improve compliance. Geriatrics. 1993;48(4):6366, 69–70.

  • 6

    Virdis A, Giannarelli C, Fritsch Neves M, Cigarette smoking and hypertension. Curr Pharm Des. 2010;16(23):25182525.

  • 7

    Feng X, Qian Z, Zhang B, Number of cigarettes smoked per day, smoking index, and intracranial aneurysm rupture: a case–control study. Front Neurol. 2018;9:380.

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    • Export Citation
  • 8

    Coughlin SS. Recall bias in epidemiologic studies. J Clin Epidemiol. 1990;43(1):8791.

  • 9

    Bijlenga P, Gondar R, Schilling S, PHASES score for the management of intracranial aneurysm: a cross-sectional population-based retrospective study. Stroke. 2017;48(8):21052112.

    • Search Google Scholar
    • Export Citation
  • 10

    Greving JP, Wermer MJH, Brown RD, Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13(1):5966.

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  • University of Iowa Hospital and Clinics, Iowa City, IA

Response

We thank Martinez-Perez et al. for their interest in our research and feedback on our article. As noted in their response, smoking imposes serious cardiovascular risks and is known to exacerbate hypertension and atherosclerotic disease. Although a study that evaluates intracranial aneurysm growth or rupture cannot be complete without accounting for smoking, we had justifiable reasons to exclude it in our study. Smoking status sometimes is missing in the electronic medical chart (Epic Systems) under the appropriate section, and sometimes can be contradictory—i.e., the patient may be reported to be a smoker under the social factors section but reported as a nonsmoker in the care provider note (or vice versa). We acknowledge that recall bias can be present in other factors as well; however, in our study we relied on objective measures (such as documented hypertension along with the treatment and verification of the medication by the pharmacist). For the above reasons, and for the lack of smoking evaluation in other well-designed and accepted studies (such as the PHASES1), we left smoking out as a factor. In addition, as highlighted by Martinez-Perez et al., there is complex interaction between smoking, hypertension, aspirin, and other risk factors. In other words, aspirin may work better—or not work at all—on smokers. This complex interaction cannot be predicted without collecting relevant information on smoking status and frequency (dose). We acknowledge that our study was limited by not evaluating the smoking status and that future prospective studies must account for it. In concordance with Martinez-Perez et al., we counsel patients with intracranial aneurysms on the risk of smoking and do take it into consideration along with other factors described in the PHASES score. We would like to thank Martinez-Perez et al. once again for their letter, which highlighted the limitations of our study and allowed us to further clarify and avoid misguiding the readers. Smoking is a risk factor worth evaluating in intracranial aneurysms, and the finding that aspirin halted growth in small unruptured aneurysms needs to be validated in prospective well-designed studies.

References

1

Bijlenga P, Gondar R, Schilling S, PHASES score for the management of intracranial aneurysm: a cross-sectional population-based retrospective study. Stroke. 2017;48(8):21052112.

  • Search Google Scholar
  • Export Citation

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Contributor Notes

Correspondence Luis Rafael Moscote-Salazar: rafaelmoscote21@gmail.com.

INCLUDE WHEN CITING Published online March 6, 2020; DOI: 10.3171/2020.1.JNS2049.

Disclosures The authors report no conflict of interest.

  • 1

    Zanaty M, Roa JA, Nakagawa D, Aspirin associated with decreased rate of intracranial aneurysm growth [published online October 29, 2019]. J Neurosurg. doi:10.3171/2019.6.JNS191273

    • Search Google Scholar
    • Export Citation
  • 2

    Starke RM, Chalouhi N, Ding D, Hasan DM. Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage. Cerebrovasc Dis. 2015;39(5–6):332342.

    • Search Google Scholar
    • Export Citation
  • 3

    Russo NW, Petrucci G, Rocca B. Aspirin, stroke and drug-drug interactions. Vascul Pharmacol. 2016;87:1422.

  • 4

    Hudson JS, Marincovich AJ, Roa JA, Aspirin and intracranial aneurysms. Stroke. 2019;50(9):25912596.

  • 5

    Timmreck TC, Randolph JF. Smoking cessation: clinical steps to improve compliance. Geriatrics. 1993;48(4):6366, 69–70.

  • 6

    Virdis A, Giannarelli C, Fritsch Neves M, Cigarette smoking and hypertension. Curr Pharm Des. 2010;16(23):25182525.

  • 7

    Feng X, Qian Z, Zhang B, Number of cigarettes smoked per day, smoking index, and intracranial aneurysm rupture: a case–control study. Front Neurol. 2018;9:380.

    • Search Google Scholar
    • Export Citation
  • 8

    Coughlin SS. Recall bias in epidemiologic studies. J Clin Epidemiol. 1990;43(1):8791.

  • 9

    Bijlenga P, Gondar R, Schilling S, PHASES score for the management of intracranial aneurysm: a cross-sectional population-based retrospective study. Stroke. 2017;48(8):21052112.

    • Search Google Scholar
    • Export Citation
  • 10

    Greving JP, Wermer MJH, Brown RD, Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13(1):5966.

    • Search Google Scholar
    • Export Citation
  • 1

    Bijlenga P, Gondar R, Schilling S, PHASES score for the management of intracranial aneurysm: a cross-sectional population-based retrospective study. Stroke. 2017;48(8):21052112.

    • Search Google Scholar
    • Export Citation

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